Transcriptional and posttranscriptional control of c-myc gene expression in WEHI 231 cells

Incubation of WEHI 231 cells, derived from a murine B-cell lymphoma, with antisera directed against its surface immunoglobulin results in the inhibition of growth within 24 h. Previously, we demonstrated that this treatment selectively affects cytoplasmic levels of c-myc mRNA (J. E. McCormack, V. H. Pepe, R. B. Kent, M. Dean, A. Marshak-Rothstein, and G. E. Sonenshein, Proc. Natl. Acad. Sci. USA 81:5546-5550, 1984). An initial increase in the cytoplasmic mRNA level is followed by a precipitous drop. We now show that the early increase results from a dramatic increase in the rate of c-myc gene transcription, as well as from partial stabilization of the mRNA in the cytoplasm. The later decrease results from a shutdown in transcription of the c-myc gene and a return to the normal lability of the cytoplasmic c-myc mRNA. Treatment with phorbol ester, like treatment with anti-immunoglobulin sera, inhibited WEHI 231 cell growth and caused similar changes in cytoplasmic c-myc mRNA levels, which can also be related to alterations in c-myc gene transcription. These results indicate that the control of c-myc gene expression in B cells is effected through regulation at multiple levels.